载脂蛋白基因风险评分与冠状动脉钙评分零的个体发生动脉粥样硬化性心血管疾病事件的相关性：动脉粥样硬化多民族研究。
Association of polygenic risk scores with incident atherosclerotic cardiovascular disease events among individuals with coronary artery calcium score of zero: The multi-ethnic study of atherosclerosis.
机构信息
Section of Cardiology, Baylor College of Medicine, Houston, TX, United States of America.
The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, United States of America.
出版信息
Prog Cardiovasc Dis. 2022 Sep-Oct;74:19-27. doi: 10.1016/j.pcad.2022.08.003. Epub 2022 Aug 8.
BACKGROUND
Polygenic risk scores (PRS) are associated with atherosclerotic cardiovascular disease (ASCVD) events. We studied incident ASCVD among individuals with absent coronary artery calcium (CAC = 0), to investigate the association of PRS with incident ASCVD among such individuals.
METHODS
Data was used from Multi-Ethnic Study of Atherosclerosis (MESA), a prospective cohort study of participants free of clinical CVD at baseline. PRS were developed based on a literature-derived list of single-nucleotide polymorphisms (SNPs) weighted by effect size. The coronary heart disease (CHD) PRS contained 180 SNPs, and the stroke PRS had 32 SNPs. These SNPs were combined to compute an ASCVD PRS. The PRS were calculated among 3132 participants with CAC = 0. Multivariable-adjusted Cox proportional hazards models evaluated the association between each PRS (top 20% vs bottom 50%) and ASCVD.
RESULTS
The study population included 3132 individuals with CAC = 0 [mean (SD) age 58 (9) years; 63% female, 33% White, 31% Black, 12% Chinese-American, 24% Hispanic]. Over a median follow-up of 16 years, there were 108 incident CHD events and 93 stroke events. ASCVD event rates were generally <7.5 per 1000-person years for all ASCVD events regardless of PRS risk stratum. The ASCVD PRS was significantly associated with incident ASCVD: (HR; 95% CI) (1.63; 1.11, 2.39). The CHD PRS was not associated with any ASCVD outcome, whereas the stroke PRS was significantly associated with ASCVD (1.84; 1.27, 2.68), CHD (1.79; 1.05, 3.06), and stroke (1.96; 1.19, 3.23). The stroke PRS results were significant among women and non-Whites.
CONCLUSIONS
Among individuals with CAC = 0, the ASCVD PRS was associated with incident ASCVD events. This appears to be driven by genetic variants related to stroke but not CHD, and particularly among women and non-Whites. ASCVD event rates remained below the threshold recommended for consideration for initiation of statin therapy even in the high PRS groups.
背景
多基因风险评分（PRS）与动脉粥样硬化性心血管疾病（ASCVD）事件相关。我们研究了无冠状动脉钙（CAC = 0）个体的 ASCVD 事件，以调查 PRS 与此类个体 ASCVD 事件的相关性。
方法
数据来自动脉粥样硬化多民族研究（MESA），这是一项基线时无临床 CVD 的参与者的前瞻性队列研究。PRS 是基于文献中与效应大小加权的单核苷酸多态性（SNP）列表开发的。冠心病（CHD）PRS 包含 180 个 SNP，中风 PRS 有 32 个 SNP。这些 SNP 被组合以计算 ASCVD PRS。在 3132 名 CAC = 0 的参与者中计算了 PRS。多变量调整的 Cox 比例风险模型评估了每个 PRS（前 20%与后 50%）与 ASCVD 之间的关系。
结果
研究人群包括 3132 名 CAC = 0 的个体[平均（SD）年龄 58（9）岁；63%为女性，33%为白人，31%为黑人，12%为华裔美国人，24%为西班牙裔]。在中位数为 16 年的随访期间，有 108 例 CHD 事件和 93 例中风事件。无论 PRS 风险分层如何，所有 ASCVD 事件的 ASCVD 事件发生率通常均<7.5/1000 人年。ASCVD PRS 与 ASCVD 事件显著相关：（HR；95%CI）（1.63；1.11，2.39）。CHD PRS 与任何 ASCVD 结局均无关，而中风 PRS 与 ASCVD（1.84；1.27，2.68）、CHD（1.79；1.05，3.06）和中风（1.96；1.19，3.23）显著相关。在女性和非白人中，中风 PRS 结果具有统计学意义。
结论
在 CAC = 0 的个体中，ASCVD PRS 与 ASCVD 事件相关。这似乎是由与中风而非 CHD 相关的遗传变异驱动的，尤其是在女性和非白人中。即使在高 PRS 组中，ASCVD 事件发生率仍低于建议开始他汀类药物治疗的阈值。
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